The long-term goal of this proposal is to understand the regulation of epithelial stem cell commitment to the sebaceous gland lineage. The sebaceous gland develops along with the hair follicle as epidermal stem cells commit to a particular lineage and differentiate. When sebaceous development is aberrant, two unsolved dermatological pathologies, acne vulgaris and human tumors, develop. Yet, despite the clinical importance of this cell lineage in human disease, little is known about how this lineage forms. My preliminary data identifies a population of unipotent progenitor cells that by expression of the transcriptional repressor, Blimpl, regulates the cellular input into the sebaceous gland and elicits premature activity of epithelial stem cells. The central hypothesis tested by this proposal is that the formation of sebaceous progenitors from hair follicle stem cells is crucial for proper formation and biology of the sebaceous gland. This hypothesis will be tested in this grant application by experiments: 1) identifying mechanisms that regulate progenitor fate by Blimpl, 2) identifying novel small molecules that regulate stem cell lineage commitment to the sebaceous gland fate, and 3) determining the role of sebaceous progenitors in communication with the stem cell compartment. Many of the cellular and molecular mechanisms will be identified during the mentored phase, and follow up on particular genes identified and cellular mechanisms will be performed in the independent phase of this proposal. Data generated from the proposed experiments will advance our understanding of the mechanisms regulating sebaceous gland development and stem cell lineage commitment in the skin. In addition, these proposed studies will potentially lead to the development of therapeutic treatments for disorders of the sebaceous gland as well as other skin disorders and cancers. [unreadable] [unreadable] [unreadable] [unreadable]